PE may be a life threatening medical event requiring hospitalization. The characteristic clinical symptoms of acute PE include acute shortness of breath, collapse-like conditions and chest pain. PE is caused by thrombosis which often occurs in femoral veins. Moreover, the thrombosis may be accompanied by further conditions such as genetically caused defects in the blood coagulation cascade or cancer.
As a consequence of thrombosis, a floating thrombus may enter and occlude the pulmonary artery. The size of the embolus determines the position of the arterial occlusion. The occlusion of a pulmonary artery results in a increased ventricular pressures and volume overload of the right heart and, as a consequence thereof, will often lead to a poor function of the left heart and circulatory failure.
PE may occur as a singular event accompanied by the aforementioned acute clinical symptoms which result, in particular in the case of emergency patients, in hospitalization or may be the result of multiple smaller PE whereby only the most recent one is accompanied with the said clinical symptoms. The latter condition is called “multiple PE” hereinafter.
Pulmonary embolism (PE) is a widespread, severe and often lethal health problem. The annual incidence for deep vein thrombosis (DVT) and PE in the general population of the Western industrialized countries may be estimated at 0.5 to 1.0 per 1000 respectively (van Beek E J R, ten Cate J W. The diagnosis of venous thromboembolism: an overview. In: Hull R D, Raskob G E, pineo G F, eds. Venous Thromboembolism: an evidence-based atlas. Armonkl: Futura Publishing Co, 1996: 93-9). There is, however, a high number of unrecognized and untreated cases, as is shown by autopsy studies. Diagnosis is difficult and hard to carry out, because PE has a wide range of clinical presentations. The most common clinical symptoms of acute PE are dyspnea, chest pain and syncope. These symptoms are similar to those of acute coronary syndrome. Approximately 30% of patients in an internal emergency unit show chest pain and respiratory symptoms, which, at first sight, point towards acute coronary syndrome. However, more than 50% of these patients do not suffer from acute coronary syndrome. The symptoms that these patients show, are related to extra-cardial causes, which are dominated by PE and other pulmonary diseases. In patients with reasonable clinical evidence for PE, first line diagnostic tests, such as ECG, chest X-ray and blood-gas analysis are indicated to assess the clinical probability of PE and the general condition of the patient. A diagnostic exclusion of PE can be made by determining the concentrations of D-dimer (a low level suggests exclusion of PE). However, elevated D-dimer levels are unspecific and are found in conditions associated with intravascular disseminated activation processes of haemostasis, like inflammatory reactions, e.g. infections or sepsis or malignous tumors. Confirmation diagnosis of PE is established by chest x-ray, lung scintigraphy, pulmonary angiography, contrast enhanced, spiral computerized tomography, and echocardiography.
It is important to initiate therapy as soon as possible. Early fatality is high and depends on the severity of the disease as well as on the existence of accompanying diseases (in particular cardiovascular diseases). Approximately 90% of the deaths occur within two hours after onset of the symptoms. The mortality of untreated PE during the hospital stay is 30%, and can be lowered to approximately 2 to 8% by applying appropriate therapies.
The treatment success substantially depends on the initiation of early therapeutic measures depending on the severity of the disease. Accordingly, in every case of a clinical suspicion of PE, this suspicion should be clarified by diagnostic and prognostic measures. The basis for this, on the other hand, is the existence of appropriate diagnostic testing parameters and testing methods, allowing the diagnostic as well as the prognostic estimation while being appropriate for emergency situations.
Due to the uncertainty about their diagnostic/prognostic value, the cardiac biomarkers troponin and natriuretic peptides were not included into therapy guidelines (anticoagulation, thrombolysis, embolectomy).
The decision about the appropriate therapy for the individual patient requires, besides the diagnosis, also risk stratification and prognosis estimation in a clinical emergency situation. When the diagnosis is certain, the essential therapeutic question is, whether anticoagulation with heparins will be sufficient, or whether additional measures, like thrombolysis or embolectomy, are necessary. Thrombolysis and embolectomy should only be used in cases of massive PE, due to the risks of complications and side effects, even when no contraindications exist.
In accordance with the actual guidelines, the hemodynamic situation of the patient is crucial for the classification into risk groups I-IV (hemodynamically stable to reanimation). While D-dimer is already established for the primary diagnosis to exclude PE, a further classification by using further markers is not possible, for the time being.
Thus, the technical problem underlying the present invention may be seen as the provision of means and methods for complying with the aforementioned needs. The technical problem is solved by the embodiments characterized in the claims and herein below.